Increased proline intake during gestation alleviates obesity-related impaired fetal development and placental function in gilts

Maternal proline (Pro) supplementation enhances fetal survival and placental development in mice. However, the effect of Pro on fetal and placental development in gilts remains to be investigated, particularly in the context of obesity-induced impaired pregnancy. Here, we investigated the effect of dietary Pro on fetal and placental development in obese gilts. Exp.1: On day 60 of gestation, forty-eight gilts with similar delivery times were selected and followed up until delivery to determine the relationship between maternal obesity, litter performance, and Pro abundance in term placentae. The results showed that impaired reproductive performance was associated with body condition parameters and inadequate placental Pro availability of gilts. Exp. 2: A total of 114 gilts were then used in a 2 × 3 factorial design to investigate the interaction between body condition (factor I: normal or obese gilts) and dietary Pro levels [factor II: low (0.89%, L-Pro), medium (1.39%, M-Pro), and high (1.89%, H-Pro)] on farrowing performance and placental angiogenesis. This resulted in six treatment combinations: normal-L-Pro, obese-L-Pro, normal-M-Pro, obese-M-Pro, normal-H-Pro, and obese-H-Pro. The effective number of replicates per group was 17, 21, 19, 21, 18, and 18, respectively (1 gilt per replicate). The results showed that increasing Pro intake increased piglet birth weight (P = 0.001), litter weight (P < 0.001), placental efficiency (P = 0.036) and placental vascular density (P < 0.001), and decreased the number of mummified fetuses (P = 0.001), the rate of low-birth-weight piglets (P = 0.005), and the rate of invalid piglets (P = 0.029). Interaction effects were observed between body condition and dietary Pro levels on piglet birth weight (P = 0.046), within-litter birth weight variation (P = 0.012), and placental vascular density (P = 0.007). Moreover, the beneficial effect of Pro on farrowing performance may be related to the improvement of sirtuin 1-superoxide dismutase 2-mitochondrial reactive oxygen species axis homeostasis and angiogenesis in the placenta. Our results suggest that gestation diets need to provide adequate Pro to meet the needs of fetal and placental development, particularly in obese gilts.